Differential effects of tumor-platelet interaction in vitro and in vivo in glioblastoma.
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Differential effects of tumor-platelet interaction in vitro and in vivo in glioblastoma. / Brockmann, Marc A; Bender, Birte; Plaxina, Elena; Nolte, Ingo; Erber, Ralf; Lamszus, Katrin; Groden, Christoph; Schilling, Lothar.
In: J NEURO-ONCOL, Vol. 105, No. 1, 1, 2011, p. 45-56.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Differential effects of tumor-platelet interaction in vitro and in vivo in glioblastoma.
AU - Brockmann, Marc A
AU - Bender, Birte
AU - Plaxina, Elena
AU - Nolte, Ingo
AU - Erber, Ralf
AU - Lamszus, Katrin
AU - Groden, Christoph
AU - Schilling, Lothar
PY - 2011
Y1 - 2011
N2 - An elevated platelet count is considered an independent predictor of short survival in glioblastoma and various other tumor entities. Prothrombotic activity of the tumor microcirculation resulting in platelet activation and release of cytokines from activated platelets has been suggested to play a role. This study was designed to analyze the effects of platelet-released cytokines on glioblastoma and endothelial cell proliferation and migration in vitro, and the influence of platelet count on glioblastoma growth and angiogenesis in vivo. In cultured human glioblastoma, umbilical cord and cerebral microvascular endothelial cells platelet-released cytokines significantly stimulated proliferation and migration as well as sprouting and formation of capillary-like structures. In vivo, glioblastoma cells were implanted in mice followed by platelet depletion starting 1 or 8 days later. Tumor volume, proliferative index, and vessel density analyzed 14 days after engraftment did not differ between animals with a normal and a low platelet count. Likewise, no effect of platelet depletion over 20 days upon the volume of intracerebrally growing tumors was observed in mice. Additionally, proliferative activity and vessel density determined in tumor samples from patients operated upon glioblastoma did not show any correlation with the patients' preoperative platelet count. Thus, we conclude that distinct proliferation- and chemotaxis-stimulating effects of platelet-derived cytokines can be achieved in vitro, while the platelet count does not exert a major influence on tumor growth and tumor angiogenesis in GBM in vivo.
AB - An elevated platelet count is considered an independent predictor of short survival in glioblastoma and various other tumor entities. Prothrombotic activity of the tumor microcirculation resulting in platelet activation and release of cytokines from activated platelets has been suggested to play a role. This study was designed to analyze the effects of platelet-released cytokines on glioblastoma and endothelial cell proliferation and migration in vitro, and the influence of platelet count on glioblastoma growth and angiogenesis in vivo. In cultured human glioblastoma, umbilical cord and cerebral microvascular endothelial cells platelet-released cytokines significantly stimulated proliferation and migration as well as sprouting and formation of capillary-like structures. In vivo, glioblastoma cells were implanted in mice followed by platelet depletion starting 1 or 8 days later. Tumor volume, proliferative index, and vessel density analyzed 14 days after engraftment did not differ between animals with a normal and a low platelet count. Likewise, no effect of platelet depletion over 20 days upon the volume of intracerebrally growing tumors was observed in mice. Additionally, proliferative activity and vessel density determined in tumor samples from patients operated upon glioblastoma did not show any correlation with the patients' preoperative platelet count. Thus, we conclude that distinct proliferation- and chemotaxis-stimulating effects of platelet-derived cytokines can be achieved in vitro, while the platelet count does not exert a major influence on tumor growth and tumor angiogenesis in GBM in vivo.
KW - Animals
KW - Humans
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Enzyme-Linked Immunosorbent Assay
KW - Cell Proliferation
KW - Blotting, Western
KW - Immunoenzyme Techniques
KW - Cell Adhesion
KW - Chemotaxis
KW - Mice, Nude
KW - Cell Movement
KW - Cytokines/metabolism
KW - Blood Platelets/metabolism/pathology
KW - Brain/cytology/metabolism
KW - Brain Neoplasms/blood supply/metabolism/pathology
KW - Endothelium, Vascular/cytology/metabolism
KW - Glioblastoma/blood supply/metabolism/pathology
KW - Neovascularization, Pathologic
KW - Platelet Activation
KW - Platelet Count
KW - Umbilical Cord/cytology/metabolism
KW - Animals
KW - Humans
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Enzyme-Linked Immunosorbent Assay
KW - Cell Proliferation
KW - Blotting, Western
KW - Immunoenzyme Techniques
KW - Cell Adhesion
KW - Chemotaxis
KW - Mice, Nude
KW - Cell Movement
KW - Cytokines/metabolism
KW - Blood Platelets/metabolism/pathology
KW - Brain/cytology/metabolism
KW - Brain Neoplasms/blood supply/metabolism/pathology
KW - Endothelium, Vascular/cytology/metabolism
KW - Glioblastoma/blood supply/metabolism/pathology
KW - Neovascularization, Pathologic
KW - Platelet Activation
KW - Platelet Count
KW - Umbilical Cord/cytology/metabolism
M3 - SCORING: Journal article
VL - 105
SP - 45
EP - 56
JO - J NEURO-ONCOL
JF - J NEURO-ONCOL
SN - 0167-594X
IS - 1
M1 - 1
ER -